PROJECT SUMMARY Noncommunicable diseases (NCDs), of which cancer is second only to cardiovascular diseases, are on the rise and are considered the next disease frontier by the WHO. While colorectal cancer (CRC) is already a public health threat in the United States, there has been an unpredicted increase in the incidence of CRCs in Low- Middle Income Countries (LMICs). Unfortunately, only 1/5th of the world?s countries report national cancer incidence and mortality estimates, with the poorest quality data from less developed countries. However, the trends point to a likely increase in disease burden in low-income countries and the need for early detection and surveillance to halt the disparate mortality rates as 70% of all CRC-related deaths occur in LMICs. Nonetheless, CRC can be addressed through prevention when resources are available. At present, the invasiveness, expense and resources required for screening colonoscopy limit its utility globally in LMICs. The understanding of CRC incidence and prevalence is limited in Africa as is the potential linkage between causes of diarrheal disease and promotion of CRC. We are conducting diarrheal surveillance in Cameroon and Tanzania, where limited information exists regarding CRC, but where data highlight that CRC is found in a younger population (<50 years old) in Tanzania, which is comparable to rates reported by other sub-Saharan African countries. This mirrors the emergence of early age onset CRC in the United States, an alarming trend. The proposed study will conduct diarrheal surveillance for pro- and anti-carcinogenic bacteria in Tanzania and two regions of Cameroon: The Littoral Region (Douala) and the Far North Region. We will characterize the bacteria present using molecular methods. In Tanzania, we will additionally conduct clinical colonoscopy and CRC resection studies to compare colonization with pro- and anti-carcinogenic bacteria, biofilms (bfs) and bacterial communities using fecal and colonoscopy biopsy specimens as well as CRC resections. Thus, this proposal will describe the molecular epidemiology of pro- and anti-carcinogenic bacteria in two countries in Africa: Tanzania and Cameroon. Herein, we test the hypothesis that the pro- and anti-carcinogenic bacterial balance and/or biofilm formation are environmental features contributing to early onset CRC. These data will be invaluable in identifying key microbial features likely relevant to the pathogenesis of human CRC. Our results will help determine if the microbial features of CRC display common elements across diverse geographic and cultural settings. Collectively, we anticipate that our results will facilitate development of CRC prevention strategies that can reach LMICs.